The overall aim of this proposal is to advance our understanding of the urinary concentrating mechanism by exploiting the knowledge obtained from the unique avian kidney model. Birds and mammals are the only vertebrates that can produce urine hyperosmotic to plasma, but structure and function of the countercurrent system for urine concentration appear to be different. In bird kidneys: 1) superficial reptilian-type (RT) and medullary mammalian-type (MT) nephrons exist; 2) an inner medulla and papilla are absent; 3) NaCl but not urea composes a corticomedullary osmotic gradient; and 4) hyposmotic drainage from RT nephrons alters urine flow and concentration. Based on these features, we propose to conduct two projects using the in vitro perfused tubule from the quail, Coturnix coturnix. Project I is to determine whether a simpler counter-current multiplication model based on NaCl transport operates between the TAL and the descending limb (DL) of the MT nephron. We will measure in the DL diffusional potentials, and permeabilities and fluxes for Na, Cl, and water. Na-K-ATPase activity of nephrons and architectural organization of the medulla will be examined. Project II aims to determine whether reductions in the volume flow rate through the collecting duct would improve urine concentrating ability in the absence of arginine vasotocin (AVT, avian antidiuretic hormone). We will measure, first, whether AVT increases osmotic water permeability and adenylate cyclase activity of the collecting duct and, second, whether a reduction of the perfusion flow rate alters net fluid transport and osmotic water permeability in the absence of AVT. Definition of the operational characteristics of the avian urinary concentrating mechanism, as compared to those of the mammalian system, will: 1) aid in clarifying fundamental problems underlying the concentrating mechanism of the mammalian kidney, and 27 provide new insights concerning common features that were necessary to adapt the primitive vertebrate kidney to permit formation of concentrated urine.